Both our work and that of other investigators have shown that protein catabolic states such as severe burn injury is accompanied by a stimulated rate of glycolysis. It is our hypothesis that this stimulated rate of glycolysis is the underlying cause of the increased loss of protein, because it elicits a suppression of protein synthesis rate via the following mechanism. Stimulation of the rate of glycolysis leads to an increased non-oxidative disposal of pyruvate, derived alanine from peripheral tissues. This reduces the availability of intracellular nitrogen (N) for glutamine synthesis, thereby causing a depletion of the intracellular glutamine pool which in turn elicits a suppression of muscle protein synthetic rate. Secondly, we will test the hypothesis that cortisol and insulin exert their effect on protein metabolism via this proposed mechanism. To test this hypothesis we will used the intact dog hindlimb model to examine the dynamics of these interrelationships by manipulating the rate of glycolysis and determining its effects on lactate and alanine fluxes across the muscle bed, intracellular glutamine concentrations and muscle protein synthesis rate. Somatostatin will be infused centrally to suppress insulin and glucagon secretion at the wholebody level and glucagon plus epinephrine infused in the femoral artery of the experimental limb at a high dose to stimulate the rate of glycolysis. Isotopes of pyruvate and leucine will be used to measure rate of glycolysis (pyruvate Ra) and muscle protein synthesis rate. These studies will help us better understand the mechanism by which protein metabolism is altered in severe stressed states.